The alpha/beta hydrolase fold common to several hydrolytic enzymes of differing phylogenetic origin and catalytic function was described by Ollis et al. (1992, Protein Eng. 5(3):197-211). The core of each enzyme in this family was described as being similar: an alpha/beta sheet of eight beta-sheets connected by alpha-helices with conserved arrangement of catalytic residues. Members of this family were found to have a catalytic triad which is borne on the conserved loop structure found in the fold. In the five members discussed in Ollis et al., the catalytic residues always occur in the same order in the primary sequence: nucleophile, acid, histidine. Furthermore, the catalytic triad residues of the members had similar topological and three dimensional positions.
Members of the hydrolase family include a hydroxylyase (Wajant, et al., 1996, J. Biol. Chem. 271(42):25830-25834) which comprises the active site motif Gly-X-Ser-X-Gly/Ala and the residues Serine 80, Aspartic 208, and Histidine 236 which are critical for enzyme activity; 2-hydroxymuconic semialdehyde hydrolase, XylF (Diaz E., 1995, J. Biol. Chem. 270(11):6403-6411), which comprises the residues Ser107, Asp228 and His 256; non-heme haloperoxidases comprises oxidases, which perform halogenation and which are related to esterases (Pelletier et al., 1995, Biochim Biophys Acta, 1995,1250(2):149-157) which comprises the residues Serine 97, Aspartic acid 229, Histidine 258; and dipeptidyl-peptidase IV (David et al., 1993, J. Biol. Chem. 268(23):17247-17252), which comprises the residues Ser624Asp702, His734).